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Specific excision of the selenocysteine tRNA[Ser]Sec (Trsp) gene in mouse liver demonstrates an essential role of selenoproteins in liver function.
J Biol Chem. 2004 Feb 27; 279(9):8011-7.JB

Abstract

Selenium is essential in mammalian embryonic development. However, in adults, selenoprotein levels in several organs including liver can be substantially reduced by selenium deficiency without any apparent change in phenotype. To address the role of selenoproteins in liver function, mice homozygous for a floxed allele encoding the selenocysteine (Sec) tRNA([Ser]Sec) gene were crossed with transgenic mice carrying the Cre recombinase under the control of the albumin promoter that expresses the recombinase specifically in liver. Recombination was nearly complete in mice 3 weeks of age, whereas liver selenoprotein synthesis was virtually absent, which correlated with the loss of Sec tRNA([Ser]Sec) and activities of major selenoproteins. Total liver selenium was dramatically decreased, whereas levels of low molecular weight selenocompounds were little affected. Plasma selenoprotein P levels were reduced by about 75%, suggesting that selenoprotein P is primarily exported from the liver. Glutathione S-transferase levels were elevated in the selenoprotein-deficient liver, suggesting a compensatory activation of this detoxification program. Mice appeared normal until about 24 h before death. Most animals died between 1 and 3 months of age. Death appeared to be due to severe hepatocellular degeneration and necrosis with concomitant necrosis of peritoneal and retroperitoneal fat. These studies revealed an essential role of selenoproteins in liver function.

Authors+Show Affiliations

Section on the Molecular Biology of Selenium, Basic Research Laboratory, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland, 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14660662

Citation

Carlson, Bradley A., et al. "Specific Excision of the Selenocysteine tRNA[Ser]Sec (Trsp) Gene in Mouse Liver Demonstrates an Essential Role of Selenoproteins in Liver Function." The Journal of Biological Chemistry, vol. 279, no. 9, 2004, pp. 8011-7.
Carlson BA, Novoselov SV, Kumaraswamy E, et al. Specific excision of the selenocysteine tRNA[Ser]Sec (Trsp) gene in mouse liver demonstrates an essential role of selenoproteins in liver function. J Biol Chem. 2004;279(9):8011-7.
Carlson, B. A., Novoselov, S. V., Kumaraswamy, E., Lee, B. J., Anver, M. R., Gladyshev, V. N., & Hatfield, D. L. (2004). Specific excision of the selenocysteine tRNA[Ser]Sec (Trsp) gene in mouse liver demonstrates an essential role of selenoproteins in liver function. The Journal of Biological Chemistry, 279(9), 8011-7.
Carlson BA, et al. Specific Excision of the Selenocysteine tRNA[Ser]Sec (Trsp) Gene in Mouse Liver Demonstrates an Essential Role of Selenoproteins in Liver Function. J Biol Chem. 2004 Feb 27;279(9):8011-7. PubMed PMID: 14660662.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Specific excision of the selenocysteine tRNA[Ser]Sec (Trsp) gene in mouse liver demonstrates an essential role of selenoproteins in liver function. AU - Carlson,Bradley A, AU - Novoselov,Sergey V, AU - Kumaraswamy,Easwari, AU - Lee,Byeong Jae, AU - Anver,Miriam R, AU - Gladyshev,Vadim N, AU - Hatfield,Dolph L, Y1 - 2003/12/04/ PY - 2003/12/9/pubmed PY - 2004/5/5/medline PY - 2003/12/9/entrez SP - 8011 EP - 7 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 279 IS - 9 N2 - Selenium is essential in mammalian embryonic development. However, in adults, selenoprotein levels in several organs including liver can be substantially reduced by selenium deficiency without any apparent change in phenotype. To address the role of selenoproteins in liver function, mice homozygous for a floxed allele encoding the selenocysteine (Sec) tRNA([Ser]Sec) gene were crossed with transgenic mice carrying the Cre recombinase under the control of the albumin promoter that expresses the recombinase specifically in liver. Recombination was nearly complete in mice 3 weeks of age, whereas liver selenoprotein synthesis was virtually absent, which correlated with the loss of Sec tRNA([Ser]Sec) and activities of major selenoproteins. Total liver selenium was dramatically decreased, whereas levels of low molecular weight selenocompounds were little affected. Plasma selenoprotein P levels were reduced by about 75%, suggesting that selenoprotein P is primarily exported from the liver. Glutathione S-transferase levels were elevated in the selenoprotein-deficient liver, suggesting a compensatory activation of this detoxification program. Mice appeared normal until about 24 h before death. Most animals died between 1 and 3 months of age. Death appeared to be due to severe hepatocellular degeneration and necrosis with concomitant necrosis of peritoneal and retroperitoneal fat. These studies revealed an essential role of selenoproteins in liver function. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/14660662/Specific_excision_of_the_selenocysteine_tRNA[Ser]Sec__Trsp__gene_in_mouse_liver_demonstrates_an_essential_role_of_selenoproteins_in_liver_function_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=14660662 DB - PRIME DP - Unbound Medicine ER -